Macrophage imaging and subset analysis using single-cell RNA sequencing

Abstract

Macrophages have been associated with drug response and resistance in diverse settings, thus raising the possibility of using macrophage imaging as a companion diagnostic to inform personalized patient treatment strategies. Nanoparticle-based contrast agents are especially promising because they efficiently deliver fluorescent, magnetic, and/or radionuclide labels by leveraging the intrinsic capacity of macrophages to accumulate nanomaterials in their role as professional phagocytes. Unfortunately, current clinical imaging modalities are limited in their ability to quantify broad molecular programs that may explain (a) which particular cell subsets a given imaging agent is actually labeling, and (b) what mechanistic role those cells play in promoting drug response or resistance. Highly multiplexed single-cell approaches including single-cell RNA sequencing (scRNAseq) have emerged as resources to help answer these questions. In this review, we query recently published scRNAseq datasets to support companion macrophage imaging, with particular focus on using dextran-based nanoparticles to predict the action of anti-cancer nanotherapies and monoclonal antibodies.

Macrophages in Acute Myeloid Leukaemia: Significant Players in Therapy Resistance and Patient Outcomes

“…An overview of TAM targeting strategies are eloquently discussed in recent review articles ( Cassetta and Pollard, 2018 ; Anfray et al, 2020 ; Lopez-Yrigoyen et al, 2020 ). Deciphering distinct macrophage populations within individual patients will be of paramount importance to guide/inform personalised treatment options, for targeting one or more immune populations alongside the main cancerous cell population ( Arlauckas et al, 2021 ). PI3K isoform-selective inhibitors are currently in pre-clinical development and/or early phase clinical trials and hold much promise for AML patients.…”

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype

“…In this 3D TME, we are able to evaluate local responses of macrophages and fibroblasts to the addition of perturbations to the system. The possible next steps would include sequentially incorporating other cell types in the 3D TME, as shown recently [ 33 ], and also capturing some features of this dynamic transition in live tumors and interaction with other tissue structures and cell types, using lineage and functional reporters [ 73 , 74 ]. Live-tumor experiments would also allow us to understand better the dynamics of the exclusion of fibroblasts.…”

The role of macrophage polarization in tendon healing and therapeutic strategies: Insights from animal models

“…This diversity is more intricately understood through advanced technologies such as single-cell RNA-seq and single-cell mass cytometry by time of flight, which allow for the analysis of macrophage phenotypes with unprecedented resolution. ( Murray, 2017 ; Arlauckas et al, 2021 ). These studies reveal that macrophages exist in a continuum of numerous subtypes, emphasizing the complexity of their roles in various physiological contexts.…”